Hypertension and diabetes, major contributors to cardiovascular disease, occur at disproportionately greater rates in African Americans. African American women, in particular, have earlier disease onset and poorer outcomes. This project will examine parameters linked with hypertension and Type 2 diabetes, and determine if relative androgen excess in African American women contributes to an accelerated disease pathway. The theoretical basis for this project integrates the concepts of insulin resistance, a major metabolic risk for cardiovascular disease; altered androgen status (excess in women), a condition which raises the risk; and endothelial dysfunction, an accelerated phase in vascular injury. In previous studies we found a strong association of insulin resistance with blood pressure (BP) level and trend, which begins at a young age. Our data in young adult African Americans indicate an upward shift in BP level as glucose tolerance deteriorates. Among women, relative androgen excess correlates with insulin resistance and higher BP. Based on additional pilot studies, our overall hypothesis for this project is that alterations in androgen status, with androgen excess in women, is a phenotype which predicts deterioration in glucose tolerance, higher BP, and expression of endothelial dysfunction in African Americans. To test this hypothesis we will use our existing database and the previously examined cohort of African Americans to conduct a longitudinal examination following an 8-year interval. The specific aims for this project are to 1) Determine if relative sex hormone status remains stable and is predictive of cardiovascular risk status in 8 years; 2) Examine the relationship of sex hormone status with glucose regulation; 3) Examine the linkage of insulin resistance with cardiovascular risk; and 4) Determine if sex hormone status contributes to endothelial dysfunction. From our database of over 500 previously examined African Americans, now age 36 to 43 years, cases will be stratified by androgen status and re-enrolled for this project. We will examine BP, glucose metabolism, insulin sensitivity, plasma lipids, sex hormones; and assess endothelial function with flow-mediated vasodilation and the vasoactive peptide endothelin-1. We have a unique and well-studied sample of pre-menopausal African American women and men on which to conduct this project. The advantage of a longitudinal assessment will enable us to delineate specific parameters that are predictive of an accelerated pathway to cardiovascular injury and poorer outcomes. The results of this project can contribute to the development of prevention and earlier intervention strategies, including more specific therapeutic targets, for this high-risk minority population.